Postdoctoral Position in Skeletal Regeneration, Diabetes, and Spatial Biology

University of Pennsylvania Perelman School of Medicine · Greater Harrisburg Area · 1 wk ago

AnalystFull-time

About the role

A postdoctoral position is available in the laboratory of Dr. Dana Graves at the University of Pennsylvania's School of Dental Medicine, Department of Periodontics, to investigate a newly identified mechanism through which diabetes impairs fracture healing and to develop a locally delivered therapeutic strategy to restore skeletal repair.

The project is supported by strong preliminary evidence demonstrating that lineage-specific deletion of FOXO1 in chondrocytes or osteoblasts reverses diabetes-impaired fracture healing. Disruption of primary cilia in these skeletal lineages reproduces defining features of defective repair in diabetes. These findings identify and strongly support a previously unrecognized FOXO1-primary cilia signaling axis as an important regulator of skeletal regeneration under diabetic conditions.

The successful candidate will define how diabetes-induced FOXO1 activity alters ciliogenesis, cellular differentiation, and regenerative signaling in chondrocytes and osteoblasts. The studies will integrate conditional mouse models targeting FOXO1, IFT80, and combined FOXO1/IFT80 deletion with fracture-healing models of type 1 and type 2 diabetes to establish the cellular and molecular events that impair skeletal regeneration. A major emphasis will be resolution of the fracture-healing microenvironment at spatial and single-cell resolution.

Experimental approaches will include 10x Genomics Xenium spatial transcriptomics, single-cell RNA sequencing, computational analysis using R and Seurat, histology, immunofluorescence, semi-automated image analysis, and microcomputed tomography.

The project also includes a translational component focused on a newly developed IGF-1 mimetic-containing nanofiber hydrogel designed for controlled local delivery at the fracture site. The candidate will examine its effects on inflammation and the sequential formation of immature mesenchymal tissue, cartilage, and bone, and determine whether the hydrogel restores cilia-dependent regenerative signaling, limits pathological FOXO1 activity, and improves structural and functional fracture healing in type 1 and type 2 diabetes.

Responsibilities

Define how diabetes-induced FOXO1 activity alters ciliogenesis, cellular differentiation, and regenerative signaling in chondrocytes and osteoblasts.
Integrate conditional mouse models targeting FOXO1, IFT80, and combined FOXO1/IFT80 deletion with fracture-healing models of type 1 and type 2 diabetes.
Resolve the fracture-healing microenvironment at spatial and single-cell resolution using 10x Genomics Xenium spatial transcriptomics and single-cell RNA sequencing.
Conduct computational analysis using R and Seurat, histology, immunofluorescence, semi-automated image analysis, and microcomputed tomography.
Examine the effects of an IGF-1 mimetic-containing nanofiber hydrogel on inflammation, tissue formation, and fracture healing in diabetic models.
Take substantial intellectual ownership of the project, including development of experimental directions and leadership of spatial-transcriptomic and computational analyses.
Present findings, prepare first-author manuscripts, and contribute to grant development and collaborative studies.

Qualifications

Applicants should hold a PhD, MD, DMD, DVM, or equivalent degree in skeletal biology, cell biology, molecular biology, bioengineering, diabetes biology, immunology, computational biology, or a related field.

Experience in one or more of the following areas is desirable: mouse genetics and disease models, bone or cartilage biology, fracture healing, spatial transcriptomics, single-cell RNA sequencing, computational analysis using R and Seurat, image analysis, molecular and cellular assays, histology, or microcomputed tomography.
Candidates with strong experimental backgrounds who wish to develop expertise in osseous and regenerative biology, spatially resolved molecular analysis, and single-cell transcriptomics are encouraged to apply.
Evidence of scientific rigor, clear scientific writing and communication, and the ability to work both independently and collaboratively.

Professional Development and Research Environment

The position provides multidisciplinary training at the interface of skeletal biology, diabetes, mouse genetics, spatial and single-cell genomics, computational biology, and translational biomaterials research. The fellow will receive direct scientific mentoring from Dr. Graves, regular project-based guidance, and opportunities to work with collaborators and shared-resource specialists across the University of Pennsylvania.

Access to Penn core facilities and collaborative expertise supporting spatial transcriptomics, single-cell genomics, imaging, histology, and quantitative analysis.
Guided training in R, Seurat, and analysis of Xenium and single-cell datasets for candidates with strong experimental backgrounds but limited computational experience.
Research plan designed to support intellectual independence, high-quality first-author publications, grant development, and preparation for subsequent faculty or industry applications.

Selected Publications

Diabetes exacerbates destructive inflammation by activating the CD137L-CD137 axis. Journal of Clinical Investigation. PMID: 41379565. Alharbi MA, Graves DT.
FOXO 1 deletion in chondrocytes rescues diabetes-impaired fracture healing by restoring angiogenesis and reducing apoptosis. PMID: 37576976. Ko KI et al.
NF-kappaB perturbation reveals unique immunomodulatory functions in Prx1-positive fibroblasts that promote development of atopic dermatitis. Science Translational Medicine. PMID: 35108061.